Stimulation and control of DNA synthesis and cell division will be studied in cultures of lymphocytes obtained from normal donors, patients with immunological diseases and patients with lymphocytic malignancies. Accurate quantitation of the number of responding cells and of cell cycle kinetics will be carried out with lymphocytes exposed to nonspecific mitogens, antigens and mixed lymphocyte cultures. Quantitation of cell kinetics and DNA synthesis, as well as qualitative analysis of newly synthesized DNA by reassociation experiments, will provide data of use in attempting to explin evidence from a variety of sources demonstrating that lymphocyte DNA synthesis may not lead to mitosis in all cases. We will continue experiments characterizing the regulatory role of steroid hormones and of agents acting through cyclic AMP in cultures of both normal and abnormal human lymphocytes. In addition, the levels of cyclic AMP, adenyl cyclase activity and phosphodiesterase activity will be measured in lymphocytes isolated from patients with autoimmune diseases and lymphocytic malignancies, and from immunosuppressed patients.